Mesothelioma is a cancer of mesothelial cells of the lungs and/or abdomen. Malignant pleural mesothelioma (MPM) is the most common form of mesothelioma and it is associated with exposure to asbestos. Currently rates of MPM are rising and estimates indicate that the incidence of MPM will peak within the next 10-15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now (Robinson B M., Ann Cardiothorac Surg 2012; 1(4):491-6; Prazakova S, Thomas P S, Sandrini A, Yates D H., Clin Respir J 2013; 8(1):1-10). Although the use of asbestos has been banned in many countries around the world, production of, and exposure to, asbestos is still present with locally high incidences of mesothelioma (Stayner L, Welch L S, Lemen R., Annu Rev Public Health 2013; 34:205-16). Carbon nanotubes have also become of potential concern for causing mesothelioma, as they have been reported to display ‘asbestos-like’ pathogenicity with mesothelioma induction potential (Donaldson K, Poland C A, Murphy F A, Macfarlane M, Chernova T, Schinwald A., Adv Drug Deliv Rev 2013; 65(15):2078-86; Dumortier H., Adv Drug Deliv Rev. 2013; 65(15):2120-26).
MPM is an extremely difficult disease to treat, with a median overall survival time ranging from 9 to 17 months, regardless of disease stage (Campbell N P, Kindler H L., Semin Respir Crit Care Med 2011; 32:102-10; Mossman B T, et al, Am J Pathol 2013; 182(4):1065-77). The combination of cisplatin and pemetrexed has been established as the current standard of care (SOC). However, only 40% of treated patients show response to this therapy, with an overall median survival of 12.1 months (Vogelzang N J, et al., J Clin Oncol 2003; 21:2636-44). Various chemotherapy agents have been used, either as monotherapy or as part of polytherapy, as a second line of treatment for MPM, but none has been successfully validated.
In Pinton, G., et al, Abstract Book of the 11th International Conference of the International Mesothelioma Interest Group, September 2012, pages 104-105, an ERβ agonist, KB9520, is described as inhibiting propagation of the human ERβ positive REN mesothelioma cell line in culture by blockage of the cell cycle at G1. In the poster to which that abstract relates, Pinton et al, presented evidence that an ERβ agonist potentiated the anti-proliferative effect of cisplatin and pemetrexed on human mesothelioma REN cells in vitro, and in vivo in mice.
There remains a need for improved or alternative treatments for clinical management of mesothelioma.